Asthma is a chronic inflammatory disease of the airways characterized by eosinophil accumulation into the lung and hyperreactivity of the airways. The disease has a wide spectrum from mild symptoms to deaths. Atopic asthma is an allergic disease where the airways-hyperreactivity is the most typical feature and occurs most often in children. When the disease occurs in older people it is very often so called intrinsic asthma. Characteristic for this subtype of asthma is a more prominent inflammation of the airways than in atopic asthma.
The most effective drugs for asthma today are inhaled corticosteroids. All currently available inhaled steroids are absorbed systemically from the lungs. The most important adverse effect of long term treatment with corticosteroids is the suppression of endogenous cortisol production by adrenals. An ideal drug for asthma would have a powerful anti-inflammatory effect locally at the airways but no systemic effects. A subset of patients with asthma are steroid-resistant. For these patients there is a need for a new drug, which does not act through the same mechanism as corticosteroids but has the same inhibitory effect on the inflammatory cells. Today methotrexate, cyclosporin and immunoglobulin are used for treatment of steroid resistant asthma. These drugs are systemically acting and thus cause serious adverse effects.
EP-A-0 440 324 discloses substituted .beta.-diketones which are suggested to be useful in the treatment of inflammatory bowel disease (IBD). The compounds of EP-A-0 440 324 were tested using the so called TNB-induced chronic colitis model in rats. The most promising compound OR 1364 (3-[(3-cyanophenyl)methylene]-2,4-pentanedione) has been extensively studied in the treatment of IBD and taken to clinical trials. Unfortunately, the trials had to be discontinued because the compound was found to be irritating.